Journal Article

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression

Li, Fan, Zhou, Lijie, Hu, Jia, Chen, Zhaohui, Deng, Zhiyao, Wang, Tao, Jiao, Xuanmao, Li, Ruizhi, Yang, Xiong, Li, Nisha, Xun, Yang, Deng, Changqi, Ding, Yuhong, Yao, Zhipeng, Lei, Yichen, Wang, Liping, Li, Heng, Ren, Shancheng, Yang, Yu, Wang, Shao-Gang, Hu, Junyi, Hou, Yaxin, Hao, Yi, Chen, Ke, Tao, Zhen, Liu, Lilong, Li, Yang, Wang, Liang, Kuang, Yingchun, Guan, Wei, Liu, Zheng

2024

Overview

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC. Multi-omic analysis of 100 clear cell renal cell carcinomas identifies four transcriptomic subgroups (IM1–IM4). IM4 is a high-risk subtype characterized by specific metabolic changes and a loss of lipid droplets.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/67/327 / 631/67/589/1588/1351 / Agriculture / Animal Genetics and Genomics / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Carcinoma, Renal Cell - genetics / Carcinoma, Renal Cell - pathology / Cell differentiation / Chromatography / Clear cell-type renal cell carcinoma / Dicyclohexylcarbodiimide / Disease Progression / Enzymes / Fibroblasts / Gene Function / Heterogeneity / Human Genetics / Humans / Immune system / Kidney cancer / Kidney Neoplasms - genetics / Kidney Neoplasms - pathology / Lipids / Lymphocytes / Mass spectrometry / Medical prognosis / Metabolic Reprogramming / Metabolism / Metabolites / Metabolomics / Multiomics / Mutation / Nephrectomy / Nutrient uptake / Patients / Prognosis / Proteomics / Scientific imaging / Spatial analysis / Trajectory analysis / Transcriptomics / Tumors